Background

Esophageal lymphoma is rare, accounting for less than 1% of all gastrointestinal lymphomas. Involvement of the esophagus is most commonly the result of contiguous spread from the proximal stomach, adjacent mediastinal lymph nodes, or cervical lymph nodes.

Primary esophageal lymphoma is even rarer. Taal et al found only 2 cases of primary involvement in their series of 37 patients with esophageal non-Hodgkin lymphoma.
[1] In another series of 1467 cases of gastrointestinal (GI) lymphoma, primary esophageal lymphoma accounted for only 3 cases. Fewer than 25 cases have been reported in the past few decades. A 2014 case report appears to be the first to describe a diagnosis of primary esophageal Burkitt lymphoma in a 17-year-old female.
[2]

Persons with esophageal lymphoma have varying presentations and a relatively poor prognosis. Invasion of the esophagus may result in hemorrhage, obstruction, or perforation with the development of a tracheoesophageal fistula. Tracheoesophageal fistula most often results in death secondary to aspiration pneumonia. Even when surgically repaired, such fistulae are likely to recur. (See Prognosis.)

Since the advent of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), esophageal lymphoma has assumed greater significance and must be considered in the differential diagnosis of immunosuppressed patients presenting with esophageal symptoms.. (See Etiology and DDx.)
[3, 4]

Primary and secondary disease

The majority of lymphomas involving the esophagus are thought to represent secondary involvement from an adjacent site. In most cases, esophageal lymphomas involving the distal esophagus represent extension from the proximal stomach.

Lymphomas arising in the middle third of the esophagus may be secondary to mediastinal lymph node enlargement with involvement of the esophagus. Another site of involvement, the proximal esophagus, may represent extension from adjacent cervical lymph nodes.

Complications

Perforation with esophagomediastinal or esophago-tracheobronchial fistula

Perforation with mediastinitis or massive hemorrhage due to invasion into the aorta or other large vessels

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Etiology

The etiology of primary GI lymphoma is unknown, but various risk factors have been recognized or proposed.

HIV infection/AIDS

HIV infection has been recognized as a risk factor for the development of primary GI lymphoma; the relative risk of developing non-Hodgkin lymphoma for persons infected with HIV is 104 times that of people who are not infected with the virus.

Epstein-Barr virus

Most of the GI tract lymphomas are of the B-cell type; however, the significance of the Epstein-Barr virus (EBV) as an etiologic factor is controversial. Although EBV is strongly related to B-cell proliferation in Burkitt lymphoma, its exact role in GI lymphoma is unknown.

Oncogenes

Deoxyribonucleic acid (DNA) probes have found the proto-oncogene C-myc transcription in 75% of AIDS-associated lymphomas, which suggests a role for the C-myc oncogene.

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Epidemiology

Occurrence in the United States

GI tract lymphoma is fairly common, making up approximately 10% of all lymphomas. In non-Hodgkin lymphoma, the most common extranodal site is the GI tract, which is involved in 5-20% of patients during life and up to 50% of patients at autopsy.
[7, 8]

The most common GI sites for lymphoma are the stomach (48-50%), small bowel (30-37%), and ileocecal region (12-13%). The esophagus is the least common site of involvement, with less than 1% of patients with GI lymphoma presenting with esophageal lymphoma.

Sex-related demographics

Because of the extreme rarity of esophageal lymphoma and the small number of reported cases, a trend cannot be established regarding which sex is more commonly affected. In one series, 12 of 17 patients were men. In another report, involving patients with HIV-associated esophageal lymphoma, the patients were typically 40-year-old men who were profoundly immunosuppressed. A final series of 6 cases of primary esophageal lymphoma included 5 men and 1 woman.

Age-related demographics

The age at presentation of esophageal lymphoma is highly variable, with cases reported in patients as young as 17 years and as old as 86 years. In one series, patients with primary esophageal lymphoma not associated with HIV infection/AIDS tended to be older (mean age, 61y) than those in the HIV infection/AIDS associated group (mean age, 40y).

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Prognosis

The data regarding the prognosis of GI lymphoma indicate a variable mortality rate. Prognosis depends on the stage of the disease at diagnosis and the feasibility of surgery or chemotherapy. Mortality also depends on the underlying health of the patient, as demonstrated by the overall poor prognoses of patients who are infected with HIV.

It has also been found that patients with T-cell lymphoma have higher rates of esophageal perforation and poorer overall survival rates than do patients demonstrating a B-cell phenotype.

Patients without HIV infection

The International Non-Hodgkin's Lymphoma Prognostic Factors Project found the following characteristics in higher-risk patients:

Age older than 60 years

Tumor stage III or IV (Ann Arbor classification)

Eastern Cooperative Oncology Group performance status of 2-4

Serum lactate dehydrogenase (LDH) levels greater than normal

Extranodal involvement of more than one site

The 5-year survival rate for patients with 0-1 of these risk factors was 73%; with 2 factors, 51%; with 3 factors, 43%; and with 4 factors, 26%.

The small number of cases of esophageal lymphoma makes predicting survival difficult. The longest reported period of disease-free survival in a person with esophageal lymphoma who was not infected with HIV is 13 years 5 months; this patient had been treated with combination chemotherapy and radiotherapy.

Patients with HIV/AIDS

Esophageal lymphoma in patients with HIV/AIDS is commonly high grade, large cell or immunoblastic, aggressive, and poorly responsive to chemotherapy. Survival rate averages have been poor (ie, 4-6 mo).

In HIV-infected persons, the presence of AIDS, a CD4 count of less than 100/µL, and a low Karnofsky score are associated with a poor prognosis.

In HIV-positive patients in a low-risk category, including those with a CD4 count of greater than 100/µL, an absence of opportunistic infections, and good performance status, response rates similar to those of HIV-negative patients may be achieved.

Maurice A Cerulli, MD Program Director, Division of Gastroenterology and Hepatology, Program in Gastroenterology at Long Island Jewish Medical Center, Associate Professor of Clinical Medicine, Albert College of Medicine